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Inhibition of vacuolar H plus ATPase enhances sensitivity to tamoxifen via up-regulation of CHOP in breast cancer cells

Title
 Inhibition of vacuolar H plus ATPase enhances sensitivity to tamoxifen via up-regulation of CHOP in breast cancer cells
Authors
 Woo Chul Noh; Young-Sun Kim; Hyun-Ah Kim; Yun-Han Lee; Hyeon-Ok Jin; Eun-Kyu Kim; Chang-Sun Hwang; Jong-Il Kim; Yoon Hwan Chang; Seok-Il Hong; Young-Jun Hong; In-Chul Park; Jin Kyung Lee
Issue Date
2013
Journal Title
 Biochemical and Biophysical Research Communications
ISSN
 0006-291X
Citation
 Biochemical and Biophysical Research Communications, Vol.437(3) : 463~468, 2013
Abstract
Resistance of estrogen receptor-positive breast cancer cells to tamoxifen represents a major barrier to the successful treatment of breast cancer. In the present study, we found that vacuolar H+ ATPase (vATPase) inhibitors, bafilomycin A1 and concanamycin A, sensitize tamoxifen-induced cell death. siRNA targeting ATP6V0C, a 16-kDa hydrophobic proteolipid subunit of vATPase that plays a central role in H+ transport, markedly increased cell death induced by tamoxifen. Interestingly, bafilomycin A1 induced up-regulation of DR4/DR5 and CHOP. Knock-down of CHOP by siRNA suppressed the cell death induced by bafilomycin A1 and tamoxifen, suggesting that bafilomycin A1-mediated CHOP activation sensitizes to tamoxifen. In addition, we found that bafilomycin A1 enhances TRAIL-induced cell death in breast cancer cells. Furthermore, we showed that combination of vATPase inhibitors with tamoxifen also effectively induced cell death in HER2- and ERα-overexpressing breast cancer cells. Overall, our results demonstrate that inhibition of vATPase can potentiate the apoptotic effects of tamoxifen through up-regulation of CHOP.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/88176
DOI
10.1016/j.bbrc.2013.06.106
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Radiation Oncology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0006291X13011169
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